PB2144: TRIAL IN PROGRESS: A PHASE 1/2 WINDOW OF OPPORTUNITY STUDY OF THE BCMAXCD3 BISPECIFIC ANTIBODY LINVOSELTAMAB IN PREVIOUSLY UNTREATED PATIENTS WITH SYMPTOMATIC MULTIPLE MYELOMA
Authors: Christopher J. Ferreri, Steven Quatela, Oluwaseun Aina, Pourab Roy, Anita Boyapati, Karen Rodriguez Lorenc, Glenn Kroog, Robert Z Orlowski
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Despite significant advances, multiple myeloma (MM) remains incurable and new therapies are needed to improve outcomes. One attractive therapeutic target for MM is the cell surface protein B-cell maturation antigen (BCMA) which is preferentially expressed on malignant plasma cells rather than normal plasma cells, activated B cells, and plasmacytoid dendritic cells (Lee, et al. Br J Haematol. 2016;176:911–22). Linvoseltamab is a BCMA×CD3 bispecific antibody capable of binding to BCMA on MM cells and CD3 on T cells, inducing T cell-mediated cytotoxicity of MM cells. Linvoseltamab monotherapy demonstrated early, deep, and durable responses with manageable safety and tolerability in patients with relapsed/refractory (R/R) MM (NCT03761108; Bumma N, et al. Blood. 2022;140(Suppl 1):10140–1). Given the single agent efficacy and tolerability of linvoseltamab in heavily pre-treated patients with R/R MM, it is hypothesized to have enhanced therapeutic benefit in patients with newly diagnosed MM (NDMM), who are thought to potentially have improved T cell fitness versus R/R patients. Aims: This open-label, Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of linvoseltamab monotherapy in patients with NDMM who are eligible or ineligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT). Methods: All patients will initially receive linvoseltamab using step-up dosing. Transplant-eligible patients will also receive linvoseltamab consolidation post-ASCT. Transplant-ineligible patients will continue linvoseltamab until disease progression or other criteria are met. There will be a window of opportunity to benefit from treatment; patients who do not meet the specified efficacy thresholds will transition to standard of care therapies. Approximately 132 patients are planned for this study. Eligibility criteria include age ≥18 years; Eastern Cooperative Oncology Group performance status 0–2; histologically or cytologically confirmed symptomatic MM; measurable disease; no prior therapy for MM, except radiation on an emergency/palliative basis or 1 month of single-agent corticosteroid if the patient still has measurable disease; and adequate bone marrow reserves, hepatic, renal, and cardiac function. The study will take place in ~30 sites located in North America and Europe. Results: Primary objectives during Phase 1 are to assess safety and tolerability of linvoseltamab and to determine a recommended regimen for Phase 2. The primary endpoints for Phase 1 are: the incidence of dose-limiting toxicities (DLTs) from the first dose of study drug to the end of the DLT observation period; the incidence and severity of treatment-emergent adverse events and adverse events of special interest with linvoseltamab through study completion. The Phase 2 objective is to assess preliminary antitumor activity as measured by the proportion of patients with very good partial response or better (determined by the investigator using International Myeloma Working Group response criteria) and the proportion of patients achieving minimal residual disease-negative status (at 10-5). Secondary objectives are to evaluate the PK properties and immunogenicity of linvoseltamab as well as soluble BCMA concentrations in serum at baseline and over time. Summary/Conclusion: This Phase 1/2 study will assess the safety, tolerability, and preliminary antitumor activity of the BCMA×CD3 bispecific antibody linvoseltamab in NDMM patients.Keywords: Multiple myeloma, Monoclonal antibody, Bispecific, Phase I/II